Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective To systematically evaluate the clinical effect of transcutaneous electrical acupoint stimulation(TEAS)on promoting postoperative gastrointestinal function recovery.Methods Randomized controlled trials(RCTs)related to postoperative gastrointestinal function using TEAS were re-trieved from the CNKI,WanFang,VIP,Embase,and PubMed database.RCTs on the effects of TEAS on postoperative gastrointestinal function were included.Methodological quality was evaluated using the quality evaluation tools recommended in Cochrane evaluation manual 5.1.Meta-analysis was performed using Rev-Man 5.3 and Stata 15.Results Thirty-four RCTs involving 3 593 patients were included.There were 1 781 patients in the TEAS group and 1 812 patients in the non-TEAS group.Compared with the non-TEAS group,the incidence of nausea(RR = 0.46,95%CI 0.36 to 0.59,P＜0.001)and vomiting(RR = 0.47,95%CI 0.37 to 0.59,P＜0.001)within 24 hours after surgery was significantly reduced in the TEAS group,and the postoperative recovery time of bowel sound(MD =-6.42 hours,95%CI-8.53 to-4.32 hours,P＜0.001),first exhaust time(MD =-8.72 hours,95%CI-10.64 to-6.80 hours,P＜0.001),andfirstdefecationtime(MD =-11.83hours,95%CI-14.67 to-8.98 hours,P＜0.001)were significantly shortened.Conclusion TEAS can promote postoperative gastrointestinal function recovery,significantly reducing the incidence of postoperative nausea and vomiting within 24 hours after sur-gery,and shortening the time of first anal exhaust and defecation after surgery.

BACKGROUND:Trunk pressure biofeedback is considered a reliable indicator for assessing core muscle strength.It not only reflects the status of an individual's trunk strength but also has a close relationship with the function of respiratory muscles. OBJECTIVE:To explore the correlation between trunk pressure biofeedback and diaphragmatic function in young adults. METHODS:A total of 80 young adults from Shangrao Normal University,China were enrolled,including 34 males and 46 females,with an average age of(19.83±1.45)years.Diaphragmatic thickness and mobility were measured using a bedside musculoskeletal ultrasound system.Maximum inspiratory pressure was determined using a portable pulmonary function tester.Lumbar and abdominal pressures in prone and supine positions were assessed using a pressure biofeedback device.The degree of correlation between trunk pressure biofeedback and diaphragmatic function was determined using Pearson or Spearman correlation coefficients.A multivariate linear regression analysis was used to determine predictive models for diaphragmatic function. RESULTS AND CONCLUSION:Grouped by sex,age,height,body mass,trunk pressure biofeedback values,diaphragm thickness during quiet inspiration and expiration,diaphragmatic thickening ratio during quiet breathing,diaphragmatic thickness during deep inspiration and expiration,diaphragmatic thickening ratio during deep breathing,diaphragmatic mobility during deep inspiration,and maximum inspiratory pressure were higher in the male group than the female group(all P<0.05).Grouped by physical activity level,trunk pressure biofeedback values and maximum inspiratory pressure were lower in the sedentary group than in the exercise group(both P<0.05).Both anterior and posterior trunk pressure biofeedback were significantly correlated with diaphragmatic thickness during quiet inspiration and expiration,diaphragmatic thickening ratio during quiet breathing,diaphragmatic thickness during deep inspiration and expiration,diaphragmatic thickening ratio during deep breathing,diaphragmatic mobility during deep inspiration,and maximum inspiratory pressure(all P<0.01).Anterior trunk pressure biofeedback entered the predictive model for diaphragmatic thickness during quiet inspiration(F=27.228,P<0.001),during deep inspiration(F=38.615,P<0.001),and along with age for diaphragmatic mobility during deep inspiration(F=15.408,P<0.001).Anterior trunk pressure biofeedback,body mass,and age entered the predictive model for maximum inspiratory pressure(F=22.314,P<0.001).To conclude,there is a strong correlation between trunk pressure biofeedback and diaphragmatic thickness,diaphragmatic mobility,and maximum inspiratory pressure.The rapid and simple measurement of trunk pressure biofeedback can serve as a method for screening the diaphragmatic function in healthy young adults.

Objective To evaluate the clinical application value of matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)in analyzing the homology of Acinetobacter baumannii(AB).Methods After excluding repetitive strains from multiple specimens of the same patient or environment,a total of 46 AB strains isolated from patients'sputum and environmental specimens of neurological intensive care unit(ICU)in a tertiary first-class general hospital from May 2020 to February 2021 were collected.Strains were detected by VITEK-MS mass spectrometer.Cluster analysis was performed by SARAMIS Premium software,and verified by multilocus sequence typing(MLST).Results Cluster analysis and comparison of MALDI-TOF MS and MLST found that among the 46 AB strains,39 were the type MS-a of MALDI-TOF MS,of which 22 strains were the clus-ter MT-A of MLST,including ST208(n=3),ST540(n=3),ST195(n=8),ST369(n=5),ST136(n=1),ST436(n=1)and ST1893(n=1);16 strains were MT-B,including type ST381(n=4),type ST469(n=11),and type ST938(n=1);one strain was cluster MT-C(ST1821);one strain of type MS-b was ST381;two strains of type MS-c were ST369;one strain of type MS-d was ST195;two strains of type MS-e were ST540 and ST369,respectively;one strain of type MS-f was STN1.Conclusion As a homology analysis method,MALDI-TOF MS still has certain limitations such as low consistency with MLST results,low resolution and specificity,thus cannot replace MLST technology.

Objective To investigate the effects of microsurgical varicocelectomy on testicular function and sexual function in patients with varicocele.Methods The clinical data of 90 patients with varicocele admitted to our hospital were retrospectively analyzed,and the patients were divided into the laparoscopic group(received laparoscopic varicocelectomy)and the microscopic group(received microsurgical varicocelectomy)according to different surgical methods,with 45 cases in each group.The testicular function and sexual function related indexes including sperm density,normal sperm ratio,rate of sperm motility(grades a+b),forward motility sperm rate,international index of erectile function-5(IIEF-5)score,and the levels of testosterone,follicle-stimulating hormone,luteinizing hormone,and androgen levels before and 6 months after surgery in the two groups were compared.The incidence of complications and recurrence 6 months after surgery in the two groups were counted.Results Compared with those before surgery,the sperm density,forward motility sperm rate,rate of sperm motility(grades a+b),normal sperm ratio,IIEF-5 score,testosterone level,and androgen level 6 months after surgery of patients in the two groups were significantly increased(P<0.05),and the levels of luteinizing hormone and follicle-stimulating hormone were decreased(P<0.05).Compared with the laparoscopic group,the levels of follicle-stimulating hormone and luteinizing hormone,and incidence of complications 6 months after surgery of patients in the microscopic group were decreased(P<0.05),and the levels of testosterone and androgens,and IIEF-5 score 6 months after surgery were increased(P<0.05).There was no significant difference in the recurrence rate between the two groups(P>0.05).Conclusion Microsurgical varicocelectomy can improve the testicular function and sexual function of patients with varicocele,with a low incidence of complications.

Objective:To investigate the effects of Jianpi Huatan Prescription on a rat model of polycystic ovary syndrome (PCOS) with insulin resistance (IR) induced by letrozole combined with high fat diet based on the liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK) signaling pathway; To discuss its mechanism.Methods:A total of 40 SD female rats were divided into model group (30 rats) and blank group (10 rats). The model group rats were fed with high-fat feed from the first week of modeling for 8 consecutive weeks, and from the fourth week onwards, were given a daily gavage of letrozole solution for 5 consecutive weeks; the blank group was fed normally, and from the 4th week onwards, an equal amount of sodium carboxymethyl cellulose solution was administered. After the completion of modeling, the modeling group was divided into Jianpi Huatan Prescription group, Metformin group, and model group according to random number table method. The Jianpi Huatan Prescription group and the metformin group were given corresponding drug interventions, while the other two groups were simultaneously administered an equal amount of physiological saline for a total of 4 weeks. Ovarian morphological changes were observed using HE staining; intraperitoneal glucose tolerance test (IPGTT) was used to detect glucose tolerance in rats; Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E 2), total testosterone (T), fasting blood glucose (FBG), and fasting insulin (FINS) in rats; Real time fluorescence quantitative PCR and Western blot techniques were used to detect changes in LKB1, AMPK mRNA and protein expression in the LKB1/AMPK signaling pathway of rat ovarian tissue. Results:Compared with the model group, the polycystic changes in the ovaries of rats in the Jianpi Huatan Prescription group were improved, and the growth rate of body weight decreased. The levels of FBG, FINS, HOMA-IR, and IPGTT decreased ( P<0.05 or P<0.01), while serum FSH and HDL-C levels were significantly up-regulated ( P<0.05 or P<0.01). The levels of T, LH, LH/FSH, TC, TG, and LDL-C decreased ( P<0.05 or P<0.01); The mRNA and protein expression levels of LKB1 and AMPK in ovarian tissue increased ( P<0.05). Conclusion:Jianpi Huatan Prescription can improve PCOS-IR in rats caused by the combination of letrozole and high-fat diet, regulate various levels of sex hormones, and improve glucose and lipid metabolism disorders by regulating the LKB1/AMPK signaling pathway, which has a repairing effect on polycystic ovary disease in rats.